Swiss biologists show new role for 'chaperone proteins'

Proteins are long coils of amino acids, the building blocks of life. hen first produced the proteins have an undefined shape known as a random coil.

In order to become biologically active, these random coils must fold into a three-dimensional shape, often a complex one. Incorrectly folded proteins can be either ineffective, or in some cases, toxic. Thus understanding the folding process is very important to biology and medicine, which was the aim of a team of Swiss biologists.

Chaperones and their client proteins

Chaperones are proteins that help other proteins to fold. Scientists call the proteins folded by chaperones, client proteins.

A study posted March 5 on the scientific website bioRxiv examines the role of a common bacterial chaperone, known as GroE, in the evolution of client proteins. 

Co-authors Bharat Ravi Iyengar and Andreas Wagner show how GroE, a chaperone protein found in many bacterial species, can affect the adaptive evolution of their client proteins by buffering (decreasing) deleterious mutations and potentiating (increasing) the genetic diversity of evolving proteins.

The scientists from the University of Zurich and the Swiss Institute of Bioinformatics, examined how GroE affects the evolution of green fluorescent protein (GFP) in four populations of E. coli bacteria. Using mutagenesis and selection, they coaxed the GFP to evolve in two distinct ways, either to preserve the green ancestral green characteristic, or to select for a blue (cyan) one.

The results were somewhat surprising. 

“In contrast to prevailing wisdom, we observe that GroE does not just buffer but also helps purge deleterious mutations,”  the authors reported. "In this way it helps reduce the genetic diversity of evolving populations." 

Additionally, they report, the GroE chaperone can also increase diversity in some of the mutants, as evidenced by the appearance of blue fluorescence. 

A diversity of chaperones

Chaperones can act to stabilize newly synthesized protein chains, accelerate the folding process and the refolding of mis-folded proteins. “This diversity of mechanisms is reflected in a diversity of chaperone structures,'' the authors noted. 

Prominent chaperone classes include the Hsp60 family known as the heat shock protein, Hsp 70, Hsp90 and Hsp100, which exist in both bacteria and eukaryotes (organisms with a distinct cell nucleus). 

The GroE complex is one of the major chaperones found in bacteria. But eukaryotes, also express a protein similar to GroE. This helps the proteins of their mitochondria and chloroplasts (the energy-producing organelles in the cell) to fold. 

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B.R. Iyengar & A. Wagner, GroEL/S helps purge deleterious mutations and reduce genetic diversity during adaptive protein evolution. bioRxiv (March 2021). DOI: https://doi.org/10.1101/2021.03.05.434078